The excretion of urinary kallikrein, a renal enzyme which cleaves a vasodilator kinin from kininogens, is subnormal in patients with essential hypertension and renal hypertensive rats, whereas kallikrein excretion is supranormal in patients with primary aldosteronism and DOC- salt hypertensive rats. So far as is known, kallikrein excretion is regulated primarily by adrenal mineralocorticoid activity, and as such is increased with low dietary sodium intake. These findings suggest that the renal kallikrein-kinin system could be involved in renal function and the control of systemic blood pressure. The proposed research will determine if maneuvers or disease which alter adrenal-renal function, and/or blood pressure, affect the activity of components of the renal kallikrein-kinin system and conversely, if altered kallikrein or kinin activity affect renal function and blood pressure. Kallikrein, kinins, and kininogen will be measured by radiochemical, radioimmunoassay, and bioassay methods in urine, plasma, and renal tissue. Normal volunteers and patients with hypertensive diseases, as well as hypertensive models such as spontaneously hypertensive, DOC-salt hypertensive, renal hypertensive and cadmium hypertensive rats will be used. The influence of altered sodium or potassium intake, sympathetic nervous activity, water restriction, kininase inhibition and the influence of clinical and animal hypertensive states on components of the kallikrein-kinin system will be determined. An ongoing collaborative project with S. Zinner, E. Kass, et al, of the Harvard Medical School, examining the striking relationships among blood pressure, race and kallikrein in 721 normal children will be continued. Our objectives are: 1) to continue to define the factors which influence kallikrein excretion; 2) to determine the relationships between altered kallikrein excretion and the activity of the renal kallikrein-kinin system; and 3) to begin to assess the role of this system in hypertensive disease states.